Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular nature of cancer-associated antigen, CA215 which reacts with RP215 monoclonal antibody and its unique epitope(s)was characterized. RP215 was initially selected and produced from one of 3,000 hybridomas which were generated from mice immunized with the cell extract of OC-3-VGH ovarian cancer cells. This cancer-associated antigen from various sources including cancer cell extract, shed culture medium and affinity-purified forms was analyzed by MALDI-TOF MS (Matrix Adsorption Laser Desorption Ionization-Time of Flight Mass Spectrometry), Western blot, carbohydrate profiling as well as enzyme immunoassays. The results of this study showed that CA215 is homologous to the heavy chains of human immunoglobulins with molecular sizes ranging from 50 to 70 KDa, when probed with RP215 or anti-human immunoglobulin G, A or M. Treatments of cancer cells with NaIO(4) drastically reduce RP215 binding to the carbohydrate-associated epitope(s) of CA215 located on the variable domain of the human immunoglobulin heavy chains. Further studies indicated that CA215 is predominantly expressed by cancer cells in both secreted and membrane-bound monomeric forms. The carbohydrate-associated epitope(s) with pH-sensitive immunoactivity appear to be present only in cancer cell-derived immunoglobulins, but not in normal human immunoglobulins. Compared to normal immunoglobulin G, CA215 contains a significantly higher percentage of N-acetyl and N-glycoyl neuraminic acid (28% vs. 8%) in the O-linked glycans, but a lower content of N-acetylglucosamine (28% vs. 41%) in the N-linked ones. It was concluded from this study that RP215 reacts specifically with carbohydrate-associated epitope(s) of immunoglobulin heavy chains expressed by various human cancer cells.
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PMID:Molecular identity of a pan cancer marker, CA215. 1915 77

RP215 monoclonal antibody (Mab) was initially generated against OC-3-VGH ovarian cancer cells and was shown to react with a cancer-associated carbohydrate epitope in glycoproteins designated as CA215. Additional five high affinity Mabs, designated as RCA-10, -100, -104, -110 and -111, respectively, were generated by using affinity-purified CA215 as the immunogen in this study. All RCA Mabs were found to recognize periodate-sensitive carbohydrate-associated epitope(s) and to pair with RP215 in typical sandwich enzyme immunoassays for the quantification of CA215. When compared with those of RP215, the amino acid sequence homology of the Fab regions ranged from 100% for RCA-100 to 65% for RCA-110, based on which 3 distinct Mab groups were categorized. In vitro TUNEL apoptosis and complement-dependent cytotoxicity assays were performed with these Mabs and found to have comparable inhibitory efficacy to cancer cells. Results of biochemical and immunological assays revealed that RP215, RCA-100 and RCA-10 react with the linear carbohydrate-associated epitope, whereas the others recognize the conformational form of the epitope in CA215. This study has suggested that the unique carbohydrate-associated epitope(s) is immunodominant in mice when immunized with CA215. It remains to be demonstrated if the differential anti-cancer efficacy exists among the distinct groups of these anti-CA215 Mabs.
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PMID:Carbohydrate-associated immunodominant epitope(s) of CA215. 2212 31